在这项研究中，我们深入探讨了基因毒性抗癌药物治疗对人体细胞染色质结构的影响，特别关注了柔红霉素的效应。利用Hi-C、ChIP-seq和RNA-seq技术，我们研究了柔红霉素和ICRF193对染色质结构的改变。我们的结果表明，生理相关剂量的柔红霉素导致了特定基因组区域内具有活跃启动子的Hi-C相互作用的局部减少，染色质结构的变化独立于Top2的抑制、细胞周期阻滞和差异基因表达的影响。在相互作用减少的区域内，我们发现RAD21在H3K27乙酰化峰值周围的重新分布。我们的研究还发现，发生结构改变的区域中存在共同的结构模式，包括两个相互分离的大区域。此外，柔红霉素还增加了H3K27乙酰化区域中CTCF的结合。此外，我们发现Top2依赖的化疗导致Hi-C接触距离衰减的改变，这是由直接和间接抑制剂驱动的。我们提出的模型表明，柔红霉素诱导的DNA双链断裂导致粘连蛋白在活跃转录的TAD边界上的重新分布，从而增加了绝缘能力。我们的发现凸显了基因毒性抗癌治疗对人类基因组染色质结构的重要影响。

In this study, we delve into the impact of genotoxic anticancer drug treatment on the chromatin structure of human cells, with a particular focus on the effects of doxorubicin. Using Hi-C, ChIP-seq, and RNA-seq, we explore the changes in chromatin architecture brought about by doxorubicin and ICRF193. Our results indicate that physiologically relevant doses of doxorubicin lead to a local reduction in Hi-C interactions in certain genomic regions that contain active promoters, with changes in chromatin architecture occurring independently of Top2 inhibition, cell cycle arrest, and differential gene expression. Inside the regions with decreased interactions, we detected redistribution of RAD21 around the peaks of H3K27 acetylation. Our study also revealed a common structural pattern in the regions with altered architecture, characterized by two large domains separated from each other. Additionally, doxorubicin was found to increase CTCF binding in H3K27 acetylated regions. Furthermore, we discovered that Top2-dependent chemotherapy causes changes in the distance decay of Hi-C contacts, which are driven by direct and indirect inhibitors. Our proposed model suggests that doxorubicin-induced DSBs cause cohesin redistribution, which leads to increased insulation on actively transcribed TAD boundaries. Our findings underscore the significant impact of genotoxic anticancer treatment on the chromatin structure of the human genome.